Patient-specific tumor-associated antigen presented on MHC class I (Neoantigen-MHC I)

Patient-specific tumor-associated antigens, commonly known as neoantigens, are unique peptides resulting from non-synonymous somatic mutations, insertions/deletions, or chromosomal rearrangements within a patient's tumor genome (Science, 2015). These mutated proteins are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, where they can be recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T-lymphocytes (Nature Reviews Clinical Oncology, 2021). Unlike tumor-associated self-antigens, neoantigens are absent from the normal proteome, making them ideal targets for immunotherapy as they bypass central thymic tolerance and reduce the risk of autoimmunity (NCI, 2023). Therapeutic interventions such as personalized cancer vaccines (e.g., mRNA-4157) and adoptive T-cell therapies are designed to exploit these targets to generate a highly specific and potent anti-tumor immune response (Science, 2018). The identification of these antigens typically requires integrated genomic sequencing and bioinformatic prediction of MHC binding affinity to ensure effective presentation (Nature Genetics, 2016).

Other names

NeoantigenTumor-specific antigenTSAMutation-derived antigenPatient-specific neoantigenMHC-I restricted neoantigen

Induction of a de novo or expanded T-cell response specifically against tumor cells by presenting unique, mutation-derived peptides in the context of MHC class I to CD8+ cytotoxic T-lymphocytes (Nature Reviews Clinical Oncology, 2021).